Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio

Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism

Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency - A neurometabolic disorder associated with reduced L-serine biosynthesis

3-phosphoglycerate dehydrogenase (PHGDH) deficiency is a disorder of L-serine biosynthesis that is characterized by congenital microcephaly, psychomotor retardation, and seizures. To investigate the molecular basis for this disorder, the PHGDH mRNA sequence was characterized, and six patients from four families were analyzed for sequence variations. Five patients from three different families were homozygous for a single nucleotide substitution predicted to change valine at position 490 to methionine. The sixth patient was homozygous for a valine to methionine substitution at position 425; both mutations are located in the carboxyterminal part of PHGDH. In vitro expression of these mutant proteins resulted in significant reduction of PHGDH enzyme activities. RNA-blot analysis indicated abundant expression of PHGDH in adult and fetal brain tissue. Taken together with the severe neurological impairment in our patients, the data presented in this paper suggest an important role for PHGDH activity and L-serine biosynthesis in the metabolism, development, and function of the central nervous system

Economic analyses of breast cancer control in low- and middle-income countries: a systematic review

Contains fulltext : 118333.pdf (publisher's version ) (Open Access)BACKGROUND: To support the development of global strategies against breast cancer, this study reviews available economic evidence on breast cancer control in low- and middle-income countries (LMICs). METHODS: A systematic article search was conducted through electronic scientific databases, and studies were included only if they concerned breast cancer, used original data, and originated from LMICs. Independent assessment of inclusion criteria yielded 24 studies that evaluated different kinds of screening, diagnostic, and therapeutic interventions in various age and risk groups. Studies were synthesized and appraised through the use of a checklist, designed for evaluating economic analyses. RESULTS: The majority of these studies were of poor quality, particularly in examining costs. Studies demonstrated the economic attractiveness of breast cancer screening strategies, and of novel treatment and diagnostic interventions. CONCLUSIONS: This review shows that the evidence base to guide strategies for breast cancer control in LMICs is limited and of poor quality. The limited evidence base suggests that screening strategies may be economically attractive in LMICs - yet there is very little evidence to provide specific recommendations on screening by mammography versus clinical breast examination, the frequency of screening, or the target population. These results demonstrate the need for more economic analyses that are of better quality, cover a comprehensive set of interventions and result in clear policy recommendations

Áreas de secção transversa do braço: implicações técnicas e aplicações para avaliação da composição corporal e da força dinâmica máxima Area de sección transversa del brazo: implicaciones técnicas y aplicaciones para avaliación de la composición corporal y de la fuerza dinámica máxima Arm cross-section areas: technical implications and applications for body composition and maximal dynamic strength evaluation

As áreas do tecido muscular (A MB) e do anel de gordura do braço (A GB), podem ser estimadas por medidas antropométricas. OBJETIVO: Investigar a validade e o erro intertestador da antropometria para inferência A MB e do A GB. Secundariamente, estudou-se a previsão da força dos membros superiores e tronco através da A MB. MÉTODOS: Foram voluntários para este estudo 40 adultos masculinos jovens (25 ± 6 anos; 72,6 ± 9,4kg), divididos aleatoriamente nos grupos de validade interna (VI, n = 30) e validade externa (VE, n = 10). Determinou-se para VI, através de conceitos geométricos, a área total do braço (A TB), A MB, A GB e área percentual de gordura do braço. O somatório de oito dobras cutâneas (S DC8) foi empregado como índice da adiposidade corporal. A força dos membros superiores e do tronco foi medida através da carga máxima alcançada no exercício supino reto livre (1-RM). As medidas antropométricas foram realizadas por dois avaliadores independentes. Os dados foram tratados por meio da análise de regressão, coeficiente de correlação intraclasse (ICC) e teste t de Student pareado (a < 0,05). RESULTADOS: A variância do S DC8 pode ser explicada em 93% (EPE = 14,6mm) a partir da A GB e do peso corporal. A A MB explicou em 66,1% (EPE = 9kg) a 1-RM. Não se observou diferença significativa, para o grupo VE, entre os valores medidos (84,2 ± 16,2kg) e preditos (78,4 ± 14,2kg) de 1-RM. Observou-se pouca variação entre os avaliadores para A MB (ICC = 0,99), A GB (ICC = 0,96) e A TB (ICC = 0,99). CONCLUSÃO: A antropometria pode ser empregada para inferência da A MB e do A GB, com boa concordância entre avaliadores, para estimativa da adiposidade corporal e da força dos membros superiores e tronco.<br>Las áreas del tejido muscular (A MB) y del de grosor del brazo (A GB), pueden ser estimadas por medidas antropométricas. OBJETIVO: Investigar la validación de el error inter-testeo de la antropometría para inferencia del A MB y del A GB. Secundariamente, se estudió la previsión de la fuerza de los miembros superiores y del tronco a través de la A MB. METODOS: Fueron voluntarios para este estudio 40 jóvenes masculinos (25 ± 6 años; 72,6 ± 9,4 kg), divididos aleatoriamente en los grupos de validación interna (VI, n = 30) y de validación externa (VE, n = 10). Se determinó para VI, a través de conceptos geométricos, el área total del brazo (A TB), A MB, A GB y el área porcentual de gordura de el brazo. La sumatoria de ocho pliegues cutáneos (S DC8) fue empleado como índice de la adiposidad corporal. La fuerza de los miembros superiores y del e tronco fue medida a través de la carga máxima alcanzada del ejercicio supino recto libre (1-RM). Las medidas antropométricas fueron realizadas por dos evaluadores independientes. Los datos fueron tratados por medio del análisis de regresión, con coeficiente de correlación intraclase (ICC) y el test t de Student apareado (a < 0,05). RESULTADOS: La varianza de S DC8 puede ser explicada en un 93% (EPE = 14,6 mm) a partir de A GB y del peso corporal. La A MB se explico en 66,1% (EPE = 9 kg) a 1-RM. No se observó diferencia significativa, para el grupo VE, entre los valores medidos (84,2 ± 16,2 kg) y predecidos (78,4 ± 14,2 kg) de 1-RM. Se observó poca variación entre los evaluadores para A MB (ICC = 0,99), A GB (ICC = 0,96) y A TB (ICC = 0,99). CONCLUSION: La antropometría puede ser empleada para la inferencia de la A MB y del A GB, con buena concordancia entre evaluadores, para estimar la adiposidad coporal y la fuerza de los miembros superiores del tronco.<br>Arm muscular tissue and fat ring areas can be evaluated by anthropometric measures. The objective of this study was to investigate the application of one technique that infers these areas to estimate body adiposity and the maximal strength of upper limbs and trunk, as well as its objectivity. For that, a sample of 40 healthy men (25 ± 6 years; 72.6 ± 9.4 kg) was divided in two groups: VI (n = 30) internal validation and VE (n = 10) external validation. It was determined to VI the muscle area (A MB), fat absolute area (A GB) and fat percentile upper-arm area (A PB) using the values of circumference and triceps skinfold, as well as the sum of seven and eight skinfold thickness (S8DC) and the maximal weight lifted in bench press (1-RM) by two evaluators separately (A and B). In VE only A MB and 1-RM were obtained. Multiple and simple regression analyses and Student t-test were applied (a < 0.05). The variance of S8DC was explained in 93% (EPE = 14.6 mm) from A GB and weight, the A MB explained in 66% (EPE = 9 kg) of the 1-RM variance by itself and there was no significant difference between the maximal weight measured and predicted in VE group. Satisfactory intraclass correlations between the evaluators to A MB (ICC = 0.99), A GB (ICC = 0.96) and A TB (ICC = 0.99) were also found. Therefore it may be concluded that the anthropometric technique that infers muscle and fat upper-arm areas can be used with good agreement between evaluators to estimate body adiposity and upper limbs and trunk strength